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Composite 52 week white paper Document Transcript

  • 1. Arthrex BioComposite Interference Screws for ACL and PCL Reconstruction Arthrex Research and Development Introduction Arthrex has developed a new absorbable composite Ceramics such as hydroxyapatite (HA) and Beta-tricalcium interference screw for graft fixation in ACL and PCL phosphate (ß-TCP) are commonly used as bone void filler reconstruction procedures, combining the resorbability of materials because of their excellent bone biocompatibility a biocompatible polymer with the bioactivity of a ceramic. and similarity in mineral content to natural bone. However, The BioComposite Interference Screw is a combination as seen with polymers, these materials have resorbability of 70% poly(L-lactide-co-D, L-lactide) (PLDLA) and 30% issues. HA is crystalline and has a slow resorption rate on biphasic calcium phosphate (BCP). the order of years [6], ideal for maintaining structure, but can lead to ingestion of ceramic particulates by surround- ing tissues. ß-TCP is amorphous and resorbs quickly, not Material Composition leaving enough time for new bone to replace the mate- rial in the defect site. Combining the resorption rates of Biodegradable polymeric materials such as polylac- HA and ß-TCP would be ideal. A new class of ceramic tide (PLA) and polyglycolide (PGA) have been used in materials, biphasic calcium phosphates (BCPs) [7], can orthopaedic applications since the 1970s, when sutures be created by combining HA and TCP in different ratios, made from these materials were approved for use by resulting in a range of controllable resorption profiles. the FDA. Both materials are easily degraded within the Typical commercial BCP formulations can vary in HA:ß- body - PLA into lactic acid and PGA into glycolic acid. TCP ratio from 60:40 to 20:80. The ratio of calcium to PLA is a crystalline material with a slow resorption rate, phosphorus (Ca/P) in bone and HA is 1.67, which is while PGA is amorphous and resorbs much faster. PLA considered “optimal”. Calcium-deficient BCP has a Ca/P and PGA materials can be combined in different ratios ratio lower than 1.67, which is controlled by the amount to produce poly(lactide-co-glycolide) (PLGA) polymers of HA to ß-TCP in the base material, after being sintered with variable degradation rates. PLA exists in two isomeric at a high temperature to convert the ceramic to a mixture forms, L-lactide and D-lactide. L-lactide is more com- of the two ceramics. It has been demonstrated that using monly found and semi-crystalline, while D-lactide is much a homogeneous calcium-deficient HA powder to form less common and amorphous. Even combining just these BCP as opposed to physically combining separate HA and PLA isomers alone can also alter degradation time and ß-TCP powders results in higher compressive strength mechanical strength. The 70:30 L:DL ratio in the PLDLA and less degradation in vivo [8]. Physically combining the material in our BioComposite Interference Screw results in powders might create voids in the final material, leading to retention of ½ of its tensile strength after 32 weeks and ½ the decrease in strength and increase in degradation. BCP of its shear strength after 45 weeks in vitro [1]. Implanted also has the ability to support new bone formation much pins made from 70:30 PLDLA, as in our product, were better than HA or ß-TCP alone, since studies have shown completely replaced by new bone at 36 months in vivo new bone formation without a fibrous tissue layer at earlier in an osteochondral fracture [2], while complete in vitro timepoints with BCP as opposed to HA or ß-TCP sepa- degradation occurred at about 18 months [3]. Spinal rately [9]. The 60:40 biphasic ratio of HA: ß-TCP in our cages made from the same 70:30 PLDLA were completely BioComposite Interference Screw shows good mechanical degraded in vivo by 12 months [4]; this can be attributed strength in a rabbit segmental defect model compared to to the location of the implant in the spine vs. in an osteo- pure HA [10] and shows excellent biocompatibility with- chondral defect. The degradation of PLDLA falls between out a fibrous interface in a rat calvarial defect model both poly(L-lactide-co-D-lactide) (PLDA), with a degradation with and without platelet-rich plasma (PRP) [11]. time of 12-16 months, and poly(L-lactide) (PLLA), with An osteoconductive material supports bone formation, a degradation time of 36-60 months [5]. propagation, and growth, and provides suitable mechanical 1
  • 2. strength when the right cells, growth factors, and other signals are in the vicinity. A study comparing PLDA and PLDA-ß-TCP interference screws to titanium interfer- ence screws found that the composite screws had higher pull-out strength and stiffness compared to the metallic screws [12]. Combining HA and BCP ceramics to PLA- urethane materials also results in higher dynamic modulus [13]. Another study found that as BCP content increases in PLDLA materials, ultimate tensile strength decreases, Figure 1a but is still within range for bone fixation materials [14]. A 70:30 PLDLA spinal cage, containing BCP particles in a 60:40 HA:ß-TCP ratio and combined with adipose- derived stem cells, showed new bone formation and osteo- clast activity on the BCP after 4 weeks [15], similar to what studies using these materials separately have found. If the optimal properties of PLDLA and BCP can be combined in a spinal application, as shown above, similar results can be theorized in ACL and PCL reconstruction. Arthrex vs. Our Competitors’ Composite Screws Figure 1b Table 1 shows the material composition of the Arthrex Imaging characterization of the BioComposite BioComposite Interference Screw vs. our competitors’ Interference Screw shows uniform dispersion of the ceramic composite screws. The ratio of polymer to ceramic in a material within the screw structure (Figure 2). The green composite material should be optimized for mechanical fluorescent stain represents the inorganic ceramic material strength and material behavior. Either lowering or rais- within the screw, going from the center cannulated por- ing the amount of polymer and/or ceramic material can tion of the screw, all the way down to the threads (white affect strength at the interface by making the screw brittle arrows). or pliable, or possibly increase resorption via acidosis. Polymer degradation that occurs too quickly can lead to a pH drop, therefore increasing the activity of osteoclasts [16] to resorb tissue and screw material and weaken the interface. Manufacturer Product Name Material Composition Arthrex BioComposite Interference Screw 70% PLDLA & 30% BCP Figure 2 DePuy Mitek Milagro 70% PLGA & 30% ß-TCP DePuy Mitek BioCryl 70% PLLA & 30% ß-TCP Testing found that 10 mm BioComposite Delta Screws, Smith & Nephew BioRCI-HA 95% PLLA & 5% HA using a hexalobe driver, had a lower cyclic displacement and ConMed Linvatec Matryx Self-reinforced (SR) higher loads-to-failure compared to Milagro screws (Table 2), 96/4 PLDA and ß-TCP with similar insertion torques for both. It is important to Stryker BiOsteon 75% PLLA and 25% HA note that these screws were not tested side-by-side in the ArthroCare BiLok 75% PLLA and 25% ß-TCP same study. It is also important to note that the number of Milagro screws tested was low, but the initial trend indi- Table 1 cates higher insertion torque for Milagro compared to the BioComposite Interference Screws. Controlled Solubility Milagro BioComposite Studies of the material properties of the BioComposite 10 mm (n=2) Delta 10 mm (n=6) Interference Screw show that molecular weight (MW, Insertion Torque (in-lbf) 29 ± 11 28 ± 4 Figure 1a) and inherent viscosity (IV, Figure 1b) drop Cyclic Displacement (mm) 4.6 (n=1) 3.5 ± 1.5 slowly and uniformly from time 0 up to 12 weeks; however, Yield Load-to-Failure (N) 728 (n=1) 1053 ± 378 the mechanical strength at both timepoints is equivalent. Ultimate Load-to-Failure (N) 877 ± 8 1206 ± 248 Table 2 2
  • 3. 9 mm Delta 10 mm Delta 11 mm Delta 12 mm Delta Insertion Torque (in-lbf) 26 ± 7 28 ± 4 29 ± 5 35 ± 7 Cyclic Displacement (mm) 3.7 ± .7 3.5 ± 1.5 3.6 ± .5 3.6 ± .8 Yield Load-to-Failure (N) 783 ± 207 1053 ± 378 958 ± 189 837 ± 191 Ultimate Load-to-Failure (N) 955 ± 219 1206 ± 248 1071 ± 165 1029 ± 128 Table 3 In Vitro Testing In vitro studies show similar amounts of human osteoblast adhesion after 24 hours (Figure 3a) and prolif- eration after 48 hours (Figure 3b) on the BioComposite Interference Screws vs. Milagro screws. Human osteoblasts were seeded onto all surfaces, including tissue culture poly- styrene (TCP) as a control, at a density of 20,000 cells/ cm2. Adhesion after 24 hours was determined by counting in a Coulter counter, while proliferation at 48 hours was determined by measuring thymidine incorporation. Figure 4a Figure 4b Figure 3a Figure 3b Figure 5a Animal Testing - 12 Weeks Computed tomography (CT) data indicate no sub- stantial degradation in vivo in an ovine ACL reconstruc- tion model at 12 weeks for either the BioComposite Interference Screw (Figure 4a) or the Milagro screw (Figure 4b) in a tibial insertion site. Hematoxylin and eosin (H&E) histology at 12 weeks shows a minimal inflamma- tory response for both the BioComposite Interference Screw (Figure 5a) and the Milagro screw (Figure 5b), also in a tibial insertion site. Figure 5b 3
  • 4. Animal Testing - 26 Weeks Animal Testing - 52 Weeks CT data at 26 weeks again shows no significant deg- CT data at 52 weeks at the tibial insertion site shows radation for either screw type. However, initial bone that the BioComposite Interference Screw keeps its integration at the tibial insertion site is seen with the shape and is well-integrated into cortical bone (Figure BioComposite Interference Screws (Figure 6a), while 8a), with some cancellous bone apposition. The Milagro minimal to no bone integration is seen with the Milagro screw (Figure 8B) is starting to lose its shape and does screws (Figure 6b). Histology of the tendon-bone inter- not integrate well with its surrounding bone. Histology face at the tibial insertion site shows Sharpey’s fibers (black at the tibial insertion site shows that the BioComposite arrows) between tendon and bone using the BioComposite Interference Screw has new bone (black arrow) within Interference Screws (Figure 7a), while there was close the screw site (Figure 9a), with some fibrous tissue. The direct contact without Sharpey’s fibers between the ten- Milagro screw (Figure 9b) also has a thin tract of new don and bone using the Milagro screws (Figure 7b). New bone (black arrow), along with some fibrous tissue, in the bone (black arrows) was seen within the tibial screw site screw site. In the femoral tunnel site, the BioComposite of the BioComposite Interference Screws (Figure 7c). The Interference Screw (Figure 9c) and the Milagro screw Milagro screws also have some minimal new bone within (Figure 9d) both show varying amounts of fibrous tissue the tibial screw site (Figure 7d, black arrow). Both screw at the screw-tissue interface. types also had a layer of fibrous tissue at the screw-tissue interface (not pictured). a b a b Figure 8 a b Figure 6 a b c d c d Figure 9 Figure 7 4
  • 5. References: 1. Moser et al, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 75B: 56–63, 2005. 2. Prokop et al, Journal of Biomedical Materials Research Part B Applied Biomaterials, 75B: 304–310, 2005. 3. Ignatius et al, Journal of Biomaterials Science Polymer Edition, 12:185-94, 2001. 4. Smit et al, Journal of Materials Science: Materials in Medicine, 17:1237–1244, 2006. 5. Middleton and Tipton, Biomaterials, 21: 2335-2346, 2000. 6. Itokawa et al, Biomaterials, 28: 4922–4927, 2007. 7. LeGeros et al, Journal of Materials Science: Materials in Medicine, 14: 201-209, 2003. 8. Gauthier et al, Journal of Materials Science: Materials in Medicine, 10: 199-204, 1999. 9. Daculsi et al, Journal of Materials Science: Materials in Medicine, 14: 195-200, 2003. 10. Balcik et al, Acta Biomaterialia 3: 985–996, 2007. 11. Plachokova et al, Clinical Oral Implants Research, 18: 244–251, 2007. 12. Zantop et al, Arthroscopy, 22: 1204-1210, 2006. 13. Rich et al, Journal of Biomedical Materials Research: Applied Biomaterials, 63: 346–353, 2002. 14. Bleach et al, Biomaterials, 23: 1579–1585, 2002. 15. Helder et al, Tissue Engineering, 13: 1799-1808, 2007. 16. Komarova et al, PNAS, 102: 2643-2648, 2005. ©2008, Arthrex Inc. All rights reserved. LA0150C